Unmasking Fracture Risk in Type 2 Diabetes: The Association of Longitudinal Glycemic Hemoglobin Level and Medications

Context: Fracture risk is underestimated in people with type 2 diabetes (T2D). Objective: To investigate the longitudinal relationship of glycated hemoglobin (HbA1c) and common medications on fracture risk in people with T2D. Methods: This retrospective population-based cohort study was conducted using de-identified claims and electronic health record data obtained from the OptumLabs Data Warehouse for the period January 1, 2007, to September 30, 2015. For each individual, the study was conducted within a 2-year HbA1c observation period and a 2-year fracture follow-up period. A cohort of 157 439 individuals with T2D [age≥55 years with mean HbA1c value≥6%] were selected from 4 018 250 US Medicare Advantage/Commercial enrollees with a T2D diagnosis. All fractures and fragility fractures were measured. Results: With covariates adjusted, poor glycemic control in T2D individuals was associated with an 29% increase of all fracture risk, compared with T2D individuals who had adequate glycemic control (HR: 1.29; 95% CI, 1.22-1.36). Treatment with metformin (HR: 0.88; 95% CI, 0.85-0.92) and DPP4 inhibitors (HR: 0.93; 95% CI, 0.88-0.98) was associated with a reduced all fracture risk, while insulin (HR: 1.26; 95% CI, 1.21-1.32), thiazolidinediones (HR: 1.23; 95% CI, 1.18-1.29), and meglitinides (HR: 1.12; 95% CI, 1.00-1.26) were associated with an increased all fracture risk (All P value<0.05). Bisphosphonates were associated similarly with increased fracture risk in the T2D and nondiabetic groups. Conclusion: Longitudinal 2-year HbA1c is independently associated with elevated all fracture risk in T2D individuals during a 2-year follow-up period. Metformin and DPP4 inhibitors can be used for management of T2D fracture risk.